Hepatitis A and B Vaccines

Slide 1:Hepatitis A and B Vaccines 

Sheila L. Palevsky, MD MPH Bureau of Immunization New York City Department of Health and Mental Hygiene October 26, 2006

Slide 2:Hepatitis B Virus

Epidemic jaundice described by Hippocrates in 5th century BCE Differentiated from Hepatitis A (infectious hepatitis) in the early 1940s Humans are only known host Resilient organism - may retain infectivity for at least 1 month at room temperature Hepadnaviridae family (DNA)

Slide 3:HBsAg Antigenic determinant found on the surface of the virus Not infectious; only the complete virus (Dane particle) is infectious When HBsAg is present, complete virus is also present During replication, HBV produces HBsAg in excess of that needed for production of the Dane particles HBcAg Nucleocapsid protein core of the HBV Not detectable in serum by conventional techniques Found in liver tissue of persons with acute or chronic HBV infection HBeAg A soluble protein found in the core of HBV Found in serum of person with high virus titers Anti-HBs Develops during convalescence to acute HBV or after vaccination Anti-HBc Indicates infection with HBV at an undefined time in the past Anti-HBe Associated with low infectivity of serum

Slide 4:Hepatitis B Clinical Features

Incubation period 60 -150 days (average 90 days) Nonspecific prodrome of fever, malaise, headache, myalgias At least 50% of infections asymptomatic Illness not specific for hepatitis B Most acute HBV infections in adults result in complete recovery with resultant immunity

Slide 5:Risk of Chronic HBV Carriage by Age of Infection

CDC

Slide 7:Hepatitis B Virus Infection

>300 million carriers worldwide Established cause of chronic hepatitis and cirrhosis Human carcinogen � an underlying cause of up to 80% of hepatocellular carcinomas

Slide 9:Hepatitis B Epidemiology

Reservoir Human. Endemic Transmission Bloodborne Subclinical cases transmit  Communicability 1-2 months before and after onset of symptoms Chronic carriers

Slide 10:Hepatitis B�United States, 1978-2005*

Hepatitis B vaccine licensed Year *2005 provisional total CDC Infant immunization recommended (1991) Adolescent immunization recommended (1996) Universal birth dose (2006) The reduction of reported cases in the late 1990s is not likely due to vaccine. An estimated 100k infections continue to occur annually, primarily in young adults.The reduction of reported cases in the late 1990s is not likely due to vaccine. An estimated 100k infections continue to occur annually, primarily in young adults.

Slide 11:Hepatitis B Virus Infection

In the United States: ~78,000 new infections/year >5,000 new carriers/year >1 million chronically infected ~5,000 deaths/year CDC 2001 estimates

Slide 12:In August 2003, NYC DOHMH Bureau of Communicable Disease started routinely investigating all HBcIgM reports and using the CDC case definition for acute hepatitis B.In August 2003, NYC DOHMH Bureau of Communicable Disease started routinely investigating all HBcIgM reports and using the CDC case definition for acute hepatitis B.

Slide 13:Modes of Hepatitis B Virus Transmission

Sexual Parenteral Perinatal

Slide 14:Body Fluid Concentrations of Hepatitis B Virus

High Moderate Low/Not Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breast milk

Slide 15:Transmission of Hepatitis B

Percutaneous: needlestick injury, IDU, body piercing, tattooing, inadequate sterilization Household transmission: shared objects � toothbrushes, razors, washcloths Person-to-person contact: biting, oozing lesions Institutionalized settings: biting, sexual contact Pre-chewing of food: traditional practices, chewing gum

Slide 16:High Risk Groups For Hepatitis B

Immigrants / refugees from endemic areas Children born in US to those from endemic areas Household contacts / sexual partners of those with chronic HBV Men who have sex with men Heterosexuals with multiple sexual partners Persons diagnosed with an STD Persons who trade sex for money or survival Injection drug users Inmates of long-term correctional facilities Persons receiving dialysis Healthcare workers

Slide 17:Risk Factors for Hepatitis B

CDC Sentinel Sites. 2001 data. CDC This graphic shows the distribution of risk factors in 2001. Persons with multiple sexual contacts, men who have sex with men, and sexual contact with a person known to have HBV infection account for 54 percent of cases with a known risk factor. Injection drug use accounts for 20 percent of cases. About 3 percent of cases are in people who have household contact with a person with acute or chronic hepatitis B. Fifteen years ago, health care workers accounted for 2 percent of HBV infections- 2 or 3 thousand new infections each year. Since that time, the rate of infection among health care workers has declined by 95 percent, and is now lower than the rate for the general population. Hepatitis B vaccine has made occupational HBV infection a thing of the past. This graphic shows the distribution of risk factors in 2001. Persons with multiple sexual contacts, men who have sex with men, and sexual contact with a person known to have HBV infection account for 54 percent of cases with a known risk factor. Injection drug use accounts for 20 percent of cases. About 3 percent of cases are in people who have household contact with a person with acute or chronic hepatitis B. Fifteen years ago, health care workers accounted for 2 percent of HBV infections- 2 or 3 thousand new infections each year. Since that time, the rate of infection among health care workers has declined by 95 percent, and is now lower than the rate for the general population. Hepatitis B vaccine has made occupational HBV infection a thing of the past.

Slide 18:Hepatitis B Virus Infection by Duration of High-Risk Behavior

0 3 6 9 12 15 Years at Risk 0 20 40 60 80 100 Percent infected IV drug user MSM HCWs Heterosexual CDC

Slide 19:~33% have been previously treated for an STD ~25% have been previously incarcerated ~2% were incarcerated during the incubation period

Of persons with acute hepatitis B:

Slide 20:After introduction of Hepatitis B vaccine in 1984, the rate of hepatocellular carcinoma (HCC) among cohorts of children declined by > 50% Rates of HCC in older age groups and rates of other childhood cancers remained stable or increased during this time period

Lee CL, Ko YC, Pediatrics 1997;99:351-353

Slide 22:Hepatitis B Vaccine

Slide 23:Hepatitis B Vaccine Intervals

3 dose series: dose # 1 dose # 2 at least one month after the 1st dose dose #3 at least 4 months after the 1st dose and at least 2 months after the 2nd dose For infants, the final dose not before 24 weeks of age

Slide 24: There is no need to ever start the hepatitis B vaccines series over again, no matter how long the interval between each dose!

Slide 25:Recommended Doses and Schedules of Hepatitis B Vaccines

� Two 1.0 ml doses given at one site in a four dose series 0,1,2,6 months

Slide 26:Immunogenicity and Vaccine Efficacy

Adequate antibody responses after three IM doses of Hep B vaccine >95% of those from birth to <19 years >90 of healthy adults <40 years ~90% of adults 40 <60 years 75% of adults >60 years

Slide 27:Vaccine Completion Rates and Seroconversion

Protective levels of antibodies in healthy adults <40 yrs of age: In 20-30% after one dose In 70-85% after two doses In >90% after three doses A full series of vaccine is recommended as there are no data on persistence of antibody after <3 doses of vaccine

Slide 28:Vaccine Completion Rates and Seroconversion

Factors that may play a role in lower seroconversion rates: Increased age (>40 years) Male gender Smoking Obesity Immune dysfunction ?

Slide 29:Persistence of Immunity

Immunologic memory established following vaccination Exposure to HBV results in anamnestic anti-HBs response Chronic infection rarely documented among vaccine responders

Slide 30:Vaccine Administration

Vaccine must be administered IM � doses given subcutaneously should not be counted as valid and should be repeated

Slide 31:Hepatitis B Vaccine

Booster doses are NOT routinely recommended for any age group

Slide 32:Hepatitis B Adverse Reactions in Adults

Pain at injection site: 13-29% Mild systemic complaints: 11-17% (fatigue, headache) Temperature >37.7� C: 1% Severe systemic reactions: rare

Slide 33:Hepatitis B Vaccine

Contraindications Severe allergic reaction to a vaccine component (hypersensitivity to Baker�s yeast) Severe allergic reaction following a previous dose Precaution Moderate or severe acute illness

Slide 34:Childhood/Adolescent Hepatitis B Vaccine Recommendations

All newborns prior to hospital or birthing center discharge All children All adolescents NYS PHL�2164 requires a complete series of hepatitis B vaccines for attendance in daycare / preK / K-12

Slide 35:Adult Hepatitis B: Vaccine Candidates

Men who have sex with men Heterosexuals with multiple partners Persons diagnosed with an STD Persons who trade sex for money or survival Injection drug users Inmates of long-term correctional facilities Persons receiving dialysis Persons with chronic liver disease (not HBV) Healthcare workers

Slide 36:Adult Hepatitis B: Vaccine Candidates(cont�d)

Staff of institutions for developmentally disabled Alaskan Natives, Pacific Islanders Immigrants/refugees* Adoptees, orphans, unaccompanied minors* Household members and sexual partners of HBV carriers Extended travel to areas of high endemicity Recipients of certain blood products *from countries of high or intermediate HBV endemnicity

Slide 37:Prevaccination Serologic Testing

Not indicated before routine vaccination of infants or children May be considered in persons where there is a high rate of HBV infection Injection drug users MSM Sexual contacts of persons with HBV infection Family members of HBV carriers Immigrants/refugees from endemic areas Adoptees from HBV endemic countries Pacific Islanders, Alaskan Natives

Slide 38:Postvaccination Serologic Testing

Not routinely recommended following vaccination of infants, children, adolescents, or most adults Recommended for: Infants born to HBsAg+ women Sexual partners of HBsAg+ persons Hemodialysis patients Immunodeficient persons Certain healthcare workers

Slide 39:Management of Non-response to Hepatitis B Vaccine

Complete a second series of three doses Should be given on the usual schedule of 0, 1 and 6 months Retest ~2 months after completing the second series

Slide 40:Persistent Non-response to Hepatitis B Vaccine

<5% of vaccinees do not develop anti-HBs after 6 valid doses May be nonresponder or "hyporesponder" Check HBsAg status If exposed, treat as nonresponder with postexposure prophylaxis

Slide 41:Hepatitis A

Enteric viral infection � oral fecal spread Acute disease and asymptomatic infection; no chronic infection Incubation period 15-50 days Non-specific illness; usually self-limited Age-related clinical illness Young children generally asymptomatic Teens and adults symptomatic Fulminant hepatitis A results in ~100 deaths/yr

Slide 42:GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION

CDC HAV infection prevalence is high or intermediate in the areas noted in red, blue, and green. Hepatitis A vaccine is recommended for persons who travel or work in these areas. Yellow indicates the areas where HAV infection prevalence is low (including the United States). HAV infection prevalence is very low in the areas shown in tan. Note: This slide has been generalized from available data.HAV infection prevalence is high or intermediate in the areas noted in red, blue, and green. Hepatitis A vaccine is recommended for persons who travel or work in these areas. Yellow indicates the areas where HAV infection prevalence is low (including the United States). HAV infection prevalence is very low in the areas shown in tan. Note: This slide has been generalized from available data.

Slide 44:Risk Factors Among Persons with Hepatitis A, Reported Cases, United States, 1990-2000

Unknown Other Child care 2% 10% 6% International travel 5% 45% Common source outbreak 4% Child care contact CDC sentinel counties Illicit drug users 8% 6% MSM Household and sexual contact 14% This chart shows the source of infection among reported cases over an eleven year span. As you can see, personal contact with another infected person is the most common identified risk factor. Being part of a recognized foodborne outbreak contributes only a small proportion (4%) to the total. However, we are not able to identify the source of infection for nearly half of all cases. It is likely that some of these cases whose source is unknown get their disease from unrecognized foodborne outbreaks. Furthermore, most travel-associated and many personal contact-associated cases are probably the result of foodborne transmission.This chart shows the source of infection among reported cases over an eleven year span. As you can see, personal contact with another infected person is the most common identified risk factor. Being part of a recognized foodborne outbreak contributes only a small proportion (4%) to the total. However, we are not able to identify the source of infection for nearly half of all cases. It is likely that some of these cases whose source is unknown get their disease from unrecognized foodborne outbreaks. Furthermore, most travel-associated and many personal contact-associated cases are probably the result of foodborne transmission.

Slide 45:Hepatitis A, United States

Most disease occurs in the context of community-wide outbreaks Infection transmitted from person to person in households and extended family settings Some groups at increased risk No risk factor identified in ~50% of cases Asymptomatic pediatric travelers play a role in silent transmission Between 25-50% of adults with no clear risk factor have contact with asymptomatic child Consider travel to endemic region as a risk factor

Slide 46:Hepatitis A Vaccine Recommendations

Universal vaccination at 12 - 23 months of age In NYC � vaccination of all children 12 � 59 months of age in certain communities Men who have sex with men Drug users Persons with chronic liver disease, including hepatitis C International travelers Recipients of clotting factors Persons with occupational risk

Slide 47:Hepatitis A Vaccine Recommendations

Health care workers: not routinely recommended Day care centers: not routinely recommended Plumbers and sewer workers: not routinely recommended Food handlers: may be considered based on local circumstances

Slide 48:Hepatitis A Vaccine

Two brands of vaccines: HAVRIX (GlaxoSmithKline) VAQTA (Merck) Pediatric (12 months -18 years) and adult (>19 years) formulations Vaccine licensed for use in persons aged 12 months and older Vaccines are equivalent and interchangeable 2 dose series for all ages: A minimum of 6 months between doses 

Slide 49:Duration of Protection

Persistence of antibody At least 10 years for 95-100% of adult vaccinees At least 6 years for 99% of vaccinated children Mathematical models of antibody decline suggest protective antibody levels persist for minimum of 15-25 years

Slide 50:Efficacy of Hepatitis A Vaccine After Exposure to Hepatitis A Virus

Indirect evidence Animal models Efficacy studies No cases in vaccinees > 16 days after vaccination No cases in vaccinated children at 9 years of follow-up Randomized trial comparing vaccine to no intervention Hospitalized cases Household contacts vaccinated within 8 days 79% efficacy; 95% CI 7%-95% Randomized trial comparing vaccine to IG just completed

Slide 51:Hepatitis A Serologic Testing

Pre-vaccination Not routinely indicated for children Cost-effective for Persons born or lived in high endemic areas Adults in high prevalence groups Adults >40 years Post-vaccination Not routinely indicated or recommended Not all commercially available assays are sensitive enough to detect lower (protective) levels of vaccine-induced antibody

Slide 52:Safety of Hepatitis A Vaccine

Most common side effects related to injection site Reported by 20-50% of recipients No severe adverse reactions attributed to vaccine Safety in pregnancy not determined � risk likely low

Slide 53:Contraindications and Precautions

Contraindications Severe adverse reaction to previous dose Severe allergy to a vaccine component Precaution Moderate to severe illness

Slide 54:Twinrix� (GSK)

Combination hepatitis B (adult dose) and hepatitis A vaccine (pediatric dose) Schedule: 0, 1, 6-12 months Approved for persons >18 years

Slide 55:Mixed Schedules: Twinrix and Hep A

Adult formulation single antigen HepA vaccine may be used to complete a schedule begun with Twinrix and vice versa Acceptable schedules 2 Twinrix and 1 hepatitis A (adult formulation 1 Twinrix and 2 hepatitis A (adult formulation) Maintain spacing recommended for Twinrix

Slide 56:The Citywide Immunization Registry (CIR)

The NYC DOHMH�s centralized, computerized database of immunization records Citywide implementation January 1, 1997 and extended August 18, 2005 Mandated reporting for NYC children <19 years Voluntary reporting for NYC adults >19 years (consent in their medical record) Access to the CIR for authorized health care providers, parents, legal guardians and custodians, and patients NYC Health Code sections 11.04 and (d)11.07 212-676-2323 www.nyc.gov/health/cir